Studies of multimodal gating of the sodium channel

Abstract

Chandler and Meves found that in squid axons perfused with NaF a small flow of Na+ ions persisted in the inactivated state, and that the Na+ channel therefore has more than one open state. Studies by Correa and Bezanilla on single patches in squid axons showed that such steady currents arose from reopening of the channel at a relatively low frequency. Currents with comparable properties are generated in mammalian brain cells and elsewhere. The existence of a third mode of gating was established by Patlak and Ortiz when they showed that in frog muscle fibres there were occasionally quite large bursts of late openings. Again, similar behaviour has been observed in other types of muscle and in brain cells. It is suggested that the voltage gating of all ionic channels involves a screw-helical mechanism, operating in steps each transferring unit charge. For segment S4 in domain IV of Na+ channels, three charges have to be transferred to reach the initial open state, and a fourth for fast inactivation to take place. The single late openings in the inactivated steady state may be explained by the transfer of a fifth charge in IVS4, while the larger bursts of reopening involve a modulation of the mechanism of fast inactivation.